EP1924364A1 - Dispositif d'administration transdermique enduisable a microprojections - Google Patents

Dispositif d'administration transdermique enduisable a microprojections

Info

Publication number
EP1924364A1
EP1924364A1 EP06803211A EP06803211A EP1924364A1 EP 1924364 A1 EP1924364 A1 EP 1924364A1 EP 06803211 A EP06803211 A EP 06803211A EP 06803211 A EP06803211 A EP 06803211A EP 1924364 A1 EP1924364 A1 EP 1924364A1
Authority
EP
European Patent Office
Prior art keywords
retainer
microprojection member
assembly
microprojection
patch
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06803211A
Other languages
German (de)
English (en)
Inventor
Joseph C. Trautman
Ling-Kang Tong
Doran P. Donnelly
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alza Corp
Original Assignee
Alza Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alza Corp filed Critical Alza Corp
Publication of EP1924364A1 publication Critical patent/EP1924364A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles

Definitions

  • the invention relates generally to transdermal delivery systems. More particularly, the invention relates to a microprojection member assembly adapted to penetrate the skin that can be readily coated with a biologically active agent.
  • transdermal delivery provides for a method of administering active agents that would otherwise need to be delivered via hypodermic injection or intravenous infusion.
  • Transdermal agent delivery offers improvements in both of these areas.
  • Transdermal delivery when compared to oral delivery, avoids the harsh environment of the digestive tract, bypasses gastrointestinal drag metabolism, reduces first-pass effects and avoids the possible deactivation by digestive and liver enzymes.
  • transdermal refers to delivery of an active agent (e.g., a therapeutic agent, such as a drug or an immunologically active agent, such as a vaccine) through the skin to the local tissue or systemic circulatory system without substantial cutting or penetration of the skin, such as cutting with a surgical knife or piercing the skin with a hypodermic needle.
  • an active agent e.g., a therapeutic agent, such as a drug or an immunologically active agent, such as a vaccine
  • transdermal agent flux is dependent upon the condition of the skin, the size and physical/chemical properties of the agent molecule, and the concentration gradient across the skin. Because of the low permeability of the skin to many active agents, transdermal delivery has had limited applications. This low permeability is attributed primarily to the stratum corneum, the outermost skin layer, which consists of flat, dead cells filled with keratin fibers (i.e., keratinocytes) surrounded by lipid bilayers. This highly-ordered structure of the lipid bilayers confers a relatively impermeable character to the stratum corneum.
  • scarifiers To increase transdermal diffusional agent flux, many techniques and systems have been developed to mechanically penetrate or disrupt the outermost skin layers thereby creating pathways into the skin in order to enhance the amount of agent being transdermally delivered.
  • Early vaccination devices known as scarifiers, generally included a plurality of tines or needles that were applied to the skin to and scratch or make small cuts in the area of application. The vaccine was applied either topically on the skin, such as disclosed in U.S. Patent No. 5,487,726, or as a wetted liquid applied to the scarifier tines, such as disclosed in U.S. Patent Nos. 4,453,926, 4,109,655, and 3,136,314.
  • the disclosed systems and apparatus employ piercing elements of various shapes, sizes and arrays to pierce the outermost layer (i.e., the stratum corneum) of the skin.
  • the piercing elements in some of these devices are extremely small, some having a microprojection length of only about 25-400 microns and a microprojection thickness of only about 5-50 microns.
  • a biologically active agent that is to be delivered can be coated on the microprojections or microprojection array. This eliminates the necessity of a separate physical reservoir and developing an agent formulation or composition specifically for the reservoir.
  • microprojection arrays When microprojection arrays are used to deliver a biologically active agent through the skin, consistent, complete, and repeatable penetration is desired. Manual application of a microprojection array often results in significant variation in puncture depth across the length and width of the array. In addition, manual application can result in large variations in puncture depth between applications, leading to inconsistent delivery amounts of the agent.
  • an automatic applicator can be used to cause the microprojections to pierce the stratum consistently over the length and width of the microprojection array in a highly reproducible manner.
  • U.S. Patent No. 6,855,131 which is hereby fully incorporated by reference, discloses a spring loaded applicator adapted to apply a microprojection array by impacting the array against the patient's skin.
  • the microprojection array is mounted within a retainer ring that is adapted to mate with the applicator.
  • the retainer ring allows the microprojection array to be mounted on the applicator without the need for the operator to touch the array.
  • the retainer ring disclosed in the '131 patent places the microprojection array in a recessed position. This placement makes it very difficult to coat the microprojection array with the biologically active agent after it is mounted in the retainer. It would thus be desirable to provide a microprojection array and retainer assembly that facilitates coating the microprojection array after it is mounted on the retainer. [00013] It is therefore an object of the present invention to provide a microprojection member or array and retainer assembly that substantially reduces or eliminates the aforementioned drawbacks and disadvantages associated with prior art microprojection devices.
  • a transdermal delivery assembly of the present invention generally includes a microprojection member having top and bottom surfaces and a plurality of stratum corneum-piercing microprojections that project from the bottom surface of the microprojection member, and a retainer having first and second ends and a central opening, wherein the microprojection member is secured to the retainer within the central opening and wherein the microprojection member is positioned adjacent the first end of the retainer so that at least a portion of the microprojections extend beyond a plane formed by the first end of the retainer.
  • the assembly also comprises an adhesive patch, wherein the microprojection member is secured to the patch and the patch is secured to the retainer.
  • the patch is secured to the retainer by frangible tabs.
  • the patch has first and second sides and the microprojection member is secured to the first side.
  • the same adhesive used to secure the microprojection member and to adhere to the patient's skin is used to secure the patch to the retainer.
  • the patch is secured to the retainer by a separate adhesive on the second side.
  • the first end of the retainer is configured to nest with the second end of the retainer so that a plurality of retainers having mounted microprojection members can be stacked.
  • the microprojection member is secured to the retainer so that the microprojection member does not contact adjacent microprojection members and adhesive patches when a plurality of assemblies are stacked.
  • the transdermal delivery assembly also includes a housing having first and second ends and a central opening, wherein the housing is adapted to receive and position the retainer within the central opening of the housing and wherein the retainer is disposed within the housing.
  • the first end of the housing is adapted to releasably attach to an impact applicator.
  • the retainer is positioned within the housing so that the microprojection member is spaced away from the first and second ends of the housing.
  • the microprojection member is coated with an agent formulation that includes at least one biologically active agent.
  • the biologically active agent is selected from the group consisting of growth hormone release hormone (GHRH), growth hormone release factor (GHPvF), insulin, insultropin, calcitonin, octreotide, endorphin, TRN, NT-36 (chemical name: N-[[(s)-4-oxo-2-azetidinyl] carbonyl]-L-histidyl-L-prolinamide), liprecin, pituitary hormones, hGH, HMG, desmopressin acetate, follicle luteoids, aANF, growth factors, growth factor releasing factor (GFRF), bMSH, GH, somatostatin, bradykinin, somatotropin, platelet-derived growth factor releasing factor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin, chorionic gonadotropin, erythropoi
  • GHRH growth hormone
  • the active agent is an immunologically active agent selected from the group consisting of proteins, polysaccharide conjugates, oligosaccharides, lipoproteins, tetanus toxoid, diphtheria toxoid, botulinum toxoid, hemaglutinins, hepatitis B surface antigen, Bordetella pertussis (recombinant PT accince — acellular), Clostridium tetani (purified, recombinant), Corynebacterium diptheriae (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cysteine protease,
  • the present invention is a method for producing a transdermal delivery assembly, including the steps of i) providing a microprojection member having top and bottom surfaces and a plurality of stratum corneum-piercing microprojections that project from the bottom surface of the microprojection member; ii) providing a retainer having first and second ends and a central opening; and iii) securing the microprojection member to the retainer within the central opening to form the transdermal delivery assembly wherein the microprojection member is positioned adjacent the first end of the retainer so that at least a portion of the microprojections extend beyond a plane formed by the first end of the retainer.
  • the method also includes the step of providing an adhesive patch and the step of securing the microprojection member to the retainer comprises securing the microprojection member to the patch and securing the patch to the retainer.
  • the method includes the step of sterilizing the transdermal delivery assembly.
  • a biocompatible coating containing at least one biologically active agent is applied to the microprojection member after the transdermal delivery assembly is sterilized.
  • the biocompatible coating is applied to the microprojection member by roller coating.
  • the biocompatible coating is applied to the microprojection member by dip-coating.
  • the noted method also includes the steps of i) providing a housing having first and second ends and a central opening, wherein the housing is adapted to receive and position the retainer within the central opening of the housing and ii) placing the retainer within the housing after applying the biocompatible coating.
  • FIGURE 1 is a front cross-sectional view of a prior art retainer
  • FIGURE 2 is a perspective view of the retainer shown in FIG. 2;
  • FIGURE 3 is an exploded view of a microprojection member assembly, according to the invention.
  • FIGURE 4 is a perspective view of the microprojection member assembly shown in FIG. 3;
  • FIGURE 5 is an exploded view of an alternate microprojection member assembly, according to the invention.
  • FIGURE 6 is a perspective view of the microprojection member assembly shown in FIG. 5;
  • FIGURE 7 is a schematic view of the microprojection member assembly shown in FIG. 4 being coated with a roller, according to the invention
  • FIGURE 8 is a perspective view illustrating microprojection member assemblies of the type shown in FIG. 6 in a stacked configuration, according to the invention
  • FIGURE 9 is an exploded view of the microprojection member assembly of the type shown in FIG. 4 also including a housing, according to the invention
  • FIGURE 10 is a perspective view of the microprojection member assembly shown in FIG. 7;
  • FIGURE 11 is a perspective view of a portion of one example of a microprojection member, according to the invention.
  • transdermal means the delivery of an agent into and/or through the skin for local or systemic therapy.
  • transdermal thus means and includes intracutaneous, intradermal and intraepidermal delivery of an agent, such as a peptide, into and/or through the skin via passive diffusion as well as energy- based diffiisional delivery, such as iontophoresis and phonophoresis.
  • transdermal flux means the rate of transdermal delivery.
  • active agent refers to a composition of matter or mixture containing a drug which is pharmacologically or biologically effective when administered in a therapeutically effective amount.
  • agent is also intended to have its broadest interpretation and is used to include any therapeutic agent or drug.
  • drug refers to any therapeutically active substance that is delivered to a living organism to produce a desired, usually beneficial, effect.
  • the biologically active agents of the invention can also be in various forms, such as free bases, acids, charged or uncharged molecules, components of molecular complexes or nonirritating, pharmacologically acceptable salts. Further, simple derivatives of the active agents (such as ethers, esters, amides, etc.) which are easily hydrolyzed at body pH, enzymes, etc., can be employed.
  • co-delivering means that a supplemental agent(s) is administered transdermally either before the primary active agent is delivered, before and during transdermal flux of the active agent, during transdermal flux of the active agent, during and after transdermal flux of the active agent, and/or after transdermal flux of the active agent.
  • microprojections refers to piercing elements which are adapted to pierce or cut through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, of the skin of a living animal, particularly, a mammal and, more particularly;, a human.
  • microprojection member generally connotes a microprojection array comprising a plurality of microprojections arranged in an array for piercing the stratum corneum.
  • the microprojection member can be formed by etching or punching a plurality of microprojections from a thin sheet and folding or bending the microprojections out of the plane of the sheet to form a configuration, such as that shown in Fig. 11.
  • the microprojection member can also be formed in other known manners, such as by forming one or more strips having microprojections along an edge of each of the strip(s) as disclosed in U.S. Patent No. 6,050,988, which is hereby incorporated by reference in its entirety.
  • coating formulation is meant to mean and include a freely flowing composition or mixture that is employed to coat the microprojections and/or arrays thereof.
  • the active agent if disposed therein, can be in solution or suspension in the formulation.
  • biocompatible coating and “solid coating”, as used herein, is meant to mean and include a “coating formulation” in a substantially solid state.
  • vasoconstrictor refers to a composition of matter or mixture that narrows the lumen of blood vessels and, hence, reduces peripheral blood flow.
  • suitable vasoconstrictors include, without limitation, amidephrine, cafaminol, cyclopentamine, deoxyepinephrine, epinephrine, felypressin, indanazoline, metizoline, midodrine, naphazoline, nordefrin, octodrine, orinpressin, oxymetazoline, phenylephrine, phenylethanolamine, phenylpropanolamine, propylhexedrine, pseudoephedrine, tetrahydrozoline, tramazoline, tuaminoheptane, tymazoline, vasopressin, xylometazoline and the mixtures thereof.
  • pathway patency modulator refers to a composition of matter or mixture that slows the closure of pathways in the stratum corneum formed by the microprojections.
  • suitable pathway patency modulators include, without limitation, osmotic agents (e.g., sodium chloride), zwitterionic compounds (e.g., amino acids), and anti-inflammatory agents, such as betamethasone 21 -phosphate disodium salt, triamcinolone acetonide 21-disodium phosphate, hydrocortamate hydrochloride, hydrocortisone 21 -phosphate disodium salt, methylprednisolone 21 -phosphate disodium salt, methylprednisolone 21-succinaate sodium salt, paramethasone disodium phosphate and prednisolone 21 -succinate sodium salt, and anticoagulants, such as citric acid, citrate salts (e.g., sodium citrate), dextrin sulfate sodium salt, and anticoagulants, such as cit
  • a prior art assembly 10 generally comprises a microprojection member 12 mounted in a prior art retainer 14 as shown in Figs. 1 and 2.
  • the microprojection member 12 is suspended in prior art retainer ring 14 by frangible tabs of adhesive patch 16, as described in detail in U.S. Patent No. 6,855,131, which is incorporated by reference herein in its entirety.
  • the microprojection member is applied to the patient's skin.
  • the microprojection member is applied to the patient's skin using an impact applicator, as described in Co- Pending U.S. Application No. 09/976,978, which is incorporated by reference herein in its entirety.
  • prior art retainer 14 places microprojection member 12 in a recessed position. Since the microprojection member 12 is spaced away from a plane formed by end 18 of the retainer, it is difficult or impossible to apply a coating of a biologically active agent to microprojection member 12 once it is mounted on prior art retainer 14. Therefore, the microprojection member 12 must be mounted to prior art retainer 14 after application of the biologically active agent coating. In turn, this necessitates either aseptic manufacturing conditions during the steps of mounting the microprojection member 12 to the prior art retainer 14 or terminal sterilization, both of which are expensive and time consuming requirements. Further, sterilization of the microprojection member after it is coated with the agent risks degradation.
  • the present invention overcomes these drawbacks by providing an apparatus and method that permits a microprojection member to be mounted on a retainer and then coated with a biologically active agent. Since the microprojection member and retainer can be sterilized after they are assembled and prior to coating, this minimizes the number of manufacturing steps that must be carried out under aseptic conditions after the microprojection member is coated.
  • the transdermal delivery assembly of the present invention generally comprises a microprojection member having top and bottom surfaces and a plurality of stratum corneum-piercing microprojections that project from the bottom surface of the microprojection member and a retainer having first and second ends and a central opening wherein the microprojection member is secured to the retainer within the central opening and wherein the microprojection member is positioned adjacent the first end of the retainer so that at least a portion of the microprojections extend beyond a plane formed by the first end of the retainer.
  • a transdermal delivery assembly 20 of the present invention which generally includes a microprojection member 12, a retainer 22 and an adhesive patch 24.
  • Microprojection member 12 is secured to the patch 24 by the adhesive and patch 24 is preferably sized to contact the patient's skin around the perimeter of microprojection member 12 to help retain the microprojection member in contact with the patient after application.
  • Adhesive patch 24 preferably has tabs 26 for securing the microprojection member 12 within retainer 22. Tabs 26 are preferably frangible so that actuation of the applicator will release patch 24 from retainer 22.
  • retainer 22 has a sloped rim to facilitate contact with the tabs 26.
  • transdermal delivery assembly 30 also generally includes a microprojection member 12, a retainer 32 and an adhesive patch 34.
  • patch 34 has adhesive on one side for securing microprojection member 12 and retaining the patch on the patient's skin.
  • a separate adhesive on the other side of patch 34 secures the patch to retainer 32.
  • the portion of patch 34 that is secured to retainer 32 is minimized and comprises tabs 36, that are also preferably frangible.
  • the retainers of the present invention position the microprojection member so that at least a portion of the microprojections extend beyond a plane formed by the end of the retainer.
  • This configuration allows a biocompatible coating containing a biologically active agent to be applied to the microprojection member after it is mounted to the retainer.
  • the coating can be applied to the microprojection member by a variety of known methods.
  • the coating is only applied to those portions the microprojection member that pierce the skin.
  • a preferred coating method comprises roller coating, which employs a roller coating mechanism that similarly limits the coating to the tips of the microprojections.
  • the roller coating method is disclosed in U.S. Patent No. 6,855,372, which is incorporated by reference herein in its entirety. As discussed in detail in the noted patent, the disclosed roller coating method provides a smooth coating that is not easily dislodged from the microprojections during skin piercing.
  • Fig. 7 shows a coating of a biologically active agent formulation 40 being applied to the microprojection member 12 of transdermal delivery assembly 20 by a rotating drum 42.
  • the position of microprojection member 12 within retainer 22 allows the microprojections to come into contact with a film of agent formulation 40 carried by drum 42 without interference from retainer 22.
  • Another coating method comprises dip-coating.
  • Dip-coating can be described as a means to coat the microprojections by partially or totally immersing the microprojections into a coating formulation. By use of a partial immersion technique, it is possible to limit the coating to the tips of the microprojections.
  • microprojection member 12 can be dipped into a reservoir of the coating formulation without contacting retainer 22 (or 32) with the coating formulation.
  • a further coating method that can be employed within the scope of the present invention comprises spray coating.
  • spray coating can encompass formation of an aerosol suspension of the coating composition.
  • an aerosol suspension having a droplet size of about 10 to 200 picoliters is sprayed onto the microprojections and then dried.
  • Pattern coating can also be employed to coat the microprojections.
  • the pattern coating can be applied using a dispensing system for positioning the deposited liquid onto the microprojection surface.
  • the quantity of the deposited liquid is preferably in the range of 0.1 to 20 nanoliters/microprojection. Examples of suitable precision-metered liquid dispensers are disclosed in U.S. Patent Nos. 5,916,524; 5,743,960; 5,741,554; and 5,738,728; which are fully incorporated by reference herein.
  • Microprojection coating formulations or solutions can also be applied using ink jet technology using known solenoid valve dispensers, optional fluid motive means and positioning means which is generally controlled by use of an electric field.
  • Other liquid dispensing technology from the printing industry or similar liquid dispensing technology known in the art can be used for applying the pattern coating of this invention.
  • a further aspect of the invention allows multiple transdermal delivery assemblies 20 to be stacked as shown in Fig. 8.
  • a void is created at the opposing end.
  • retainer 22 (or 32) is configured to nest with like retainers as shown in Fig. 8.
  • microprojection member 12 and patch 24 are positioned within the void at the opposing end of the adjacent retainer, preventing the microprojection member 12 and patch 24 from coming into contact with the assembly of the adjacent retainer.
  • retainer 22 (or 32) is configured to mate with a housing 50.
  • Housing 50 preferably has opposing ends, a first end 52 adapted to attach to an impact applicator and a second end 54 that contacts the patient's skin. Also preferably, housing 50 is configured to position retainer 22 so that inadvertent contact with microprojection member 12 is minimized by spacing retainer 22 away from each end. Although microprojection member 12 must already be coated with the active agent when retainer 22 is placed within housing 50, it is relatively easy to maintain aseptic conditions for this assembly step.
  • the retainers 22 and 32 have been shown as being generally circular or ring shaped, however any suitable shape or configuration can be employed as desired so long as a central opening is defined within which the microprojection member can be secured and so that at least a portion of the microprojections extend beyond the plane formed by the end of the retainer.
  • the microprojection member 12 includes an array of microprojections 60 that project from a sheet 62.
  • the microprojections 60 preferably extend at substantially a 90° angle from the sheet 62, which in the noted embodiment includes openings 64.
  • the microprojections 60 are formed by etching or punching a plurality of microprojections 60 from a thin metal sheet 62 and bending the microprojections out of the plane of the sheet.
  • the piercing elements have a projection length less than 1000 microns. In a further embodiment, the piercing elements have a projection length of less than 500 microns, more preferably, less than 250 microns.
  • the microprojections further have a width in the range of approximately 25 - 500 microns and a thickness in the range of approximately 10 — 100 microns.
  • the microprojections may be formed in different shapes, such as needles, blades, pins, punches, and combinations thereof.
  • the microprojection member 12 has a microprojection density of at least approximately 10 microprojections/cm 2 , more preferably, in the range of at least approximately 200 - 2000 microprojections/cm 2 .
  • the number of openings per unit area through which the agent passes is at least approximately 10 openings/cm 2 and less than about 2000 openings/cm 2 .
  • the microprojections 60 preferably have a length less than 145 ⁇ m, more preferably, in the range of approximately 50 - 145 ⁇ m, even more preferably, in the range of approximately 70 - 140 ⁇ m.
  • the microprojection member 12 comprises an array preferably having a microprojection density greater than 100 microprojections/cm 2 , more preferably, in the range of approximately 200 — 3000 microprojections/cm 2 .
  • the microprojection member 12 can be manufactured from various metals, such as stainless steel, titanium, nickel titanium alloys, or similar biocompatible materials.
  • the microprojection member 12 can also be constructed out of a non-conductive material, such as a polymer.
  • the microprojection member can be coated with a non- conductive material, such as Parylene®, or a hydrophobic material, such as Teflon®, silicon or other low energy material.
  • a non- conductive material such as Parylene®
  • a hydrophobic material such as Teflon®, silicon or other low energy material.
  • the noted hydrophobic materials and associated base (e.g., photoreist) layers are set forth in U.S. Application Serial No. 60/484,142, which is incorporated by reference herein.
  • Microprojection members that can be employed with the present invention include, but are not limited to, the members disclosed in U.S. Patent Nos. 6,083,196, 6,050,988 and 6,091,975, 6,230,051 Bl, 6,322,808 and Co-Pending U.S. Application Serial No. 10/045,842, which are incorporated by reference herein in their entirety, which are incorporated by reference herein in their entirety.
  • Other microprojection members that can be employed with the present invention include members formed by etching silicon using silicon chip etching techniques or by molding plastic using etched micro-molds, such as the members disclosed U.S. Patent No. 5,879,326, which is incorporated by reference herein in its entirety.
  • the active agent to be delivered can be contained in a biocompatible coating 66 that is disposed on the microprojection member 12.
  • the microprojections 60 can further include means adapted to receive and/or enhance the volume of the coating 66, such as apertures (not shown), grooves (not shown), surface irregularities (not shown) or similar modifications, wherein the means provides increased surface area upon which a greater amount of coating can be deposited.
  • the microprojections 60 can be formed with a hook or barb 68 configured to retain microprojection member 12 in contact with the patient's skin.
  • the biologically active agent comprises an agent active in one of the major therapeutic areas including, but not limited to: anti-infectives such as antibiotics and antiviral agents; analgesics, including fentanyl, sufentanil, remifentanil, buprenorphine and analgesic combinations; anesthetics; anorexics; antiarthritics; antiasthmatic agents such as terbutaline; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antihistamines; anti-inflammatory agents; antimigraine preparations; antimotion sickness preparations such as scopolamine and ondansetron; antinauseants; antineoplastics ; antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics; antispasmodics, including gastrointestinal and urinary; anticholinergics; sympathomimetics; xanthine derivatives; cardiovascular
  • anti-infectives such as antibiotics
  • agents include, without limitation, growth hormone release hormone (GHRH), growth hormone release factor (GHRF), insulin, insultropin, calcitonin, octreotide, endorphin, TRN, NT-36 (chemical name: N-[[(s)-4- oxo-2-azetidinyl] carbonyl]-L-histidyl-L-prolinamide), liprecin, pituitary hormones (e.g., HGH 5 HMG, desmopressin acetate, etc), follicle luteoids, aANF, growth factors such as growth factor releasing factor (GFRF), bMSH, GH, somatostatin, bradykinin, somatotropin, platelet-derived growth factor releasing factor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin, chorionic gonadotropin, erythropoie
  • GHRH growth hormone
  • immunologically active agents including, without limitation, viruses, bacteria, protein-based vaccines, polysaccharide-based vaccines, proteins, polysaccharide conjugates, oligosaccharides, lipoproteins, immunogenic materials, antigenic agents and vaccine adjuvants.
  • vaccine delivery can be found in Co-Pending Application Serial Nos. 10/127,171 and 10/971,877, which are hereby incorporated in their entirety by reference.
  • Suitable immunologically active agents include, without limitation, antigens in the form of proteins, polysaccharide conjugates, oligosaccharides, and lipoproteins.
  • Specific subunit vaccines include, without limitation, tetanus toxoid, diphtheria toxoid, botulinum toxoid, hemaglutinins, hepatitis B surface antigen, Bordetella pertussis (recombinant PT accince - acellular), Clostridium tetani (purified, recombinant), Corynebacterium diphtheria (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cyste
  • nucleic acid sequences encoding for immuno-regulatory lymphokines such as IL-18, IL-2 IL-12, IL-15, IL-4, ILlO, gamma interferon, and NF kappa B regulatory signaling proteins can be used.
  • alum-adjuvanted vaccine formulations typically lose potency upon freezing and drying.
  • the noted formulations can be further processed as disclosed in Provisional Application No. 60/649,275, filed January 31, 2005; which is expressly incorporated by reference herein in its entirety.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention porte sur un dispositif d'administration transdermique à microprojections comportant un support (12) de microprojections se fixant à un rétenteur (22) s'utilisant avec un applicateur à impact, une partie au moins des microprojections s'étendant au delà d'un plan formé par l'extrémité du support. La configuration du dispositif permet d'enduire le support (12) une fois fixé au rétenteur d'un agent biologiquement actif. On réduit ainsi le nombre des étapes de fabrication devant être effectuées dans des conditions d'asepsie pour maintenir la stérilité du dispositif après l'enduisage du support de microprojections.
EP06803211A 2005-09-12 2006-09-11 Dispositif d'administration transdermique enduisable a microprojections Withdrawn EP1924364A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US71645905P 2005-09-12 2005-09-12
PCT/US2006/035047 WO2007033015A1 (fr) 2005-09-12 2006-09-11 Dispositif d'administration transdermique enduisable a microprojections

Publications (1)

Publication Number Publication Date
EP1924364A1 true EP1924364A1 (fr) 2008-05-28

Family

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EP06803211A Withdrawn EP1924364A1 (fr) 2005-09-12 2006-09-11 Dispositif d'administration transdermique enduisable a microprojections

Country Status (7)

Country Link
US (1) US20070293814A1 (fr)
EP (1) EP1924364A1 (fr)
JP (1) JP2009507576A (fr)
CN (1) CN101267896A (fr)
AU (1) AU2006291157A1 (fr)
CA (1) CA2619452A1 (fr)
WO (1) WO2007033015A1 (fr)

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Also Published As

Publication number Publication date
WO2007033015A1 (fr) 2007-03-22
CA2619452A1 (fr) 2007-03-22
US20070293814A1 (en) 2007-12-20
AU2006291157A1 (en) 2007-03-22
JP2009507576A (ja) 2009-02-26
CN101267896A (zh) 2008-09-17

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